A method for detecting protein interaction between two target proteins by using complementarity of split luciferase fragments has been recently developed (Kim, S. B., Ozawa, T., Watanabe, S., Umezawa, Y., 2004. Proc. Natl. Acad. Sci. USA. 101, 11542-11547). The method for detecting a protein-protein interaction using complementarity is generally conducted by fusing fragments of a split reporter protein respectively with the target proteins, and in this process, each fragment does not have significant activity by itself. When the target proteins interact with each other, the inactive reporter protein fragments complement with each other to regain the activity which allows emission of the signal to enable indirect tracking of the protein-protein interaction.
Such method using the complementarity has been used for various reporter proteins such as dihydrofolate reductase and β-lactamase green fluorescent protein. Also, several luciferases such as Renilla reniformis luciferase, Photinus Pyralis luciferase, red-emitting Photinus Pyralis luciferase, and green-emitting Photinus Pyralis luciferase have been used.